Public Citizen's Health Research Group is objecting to an NIH Alzheimer's prevention trial of Pfizer/Pharmacia's Celebrex and Bayer's Naprosyn on the grounds that the drugs have not demonstrated activity in preventing the disease.

"We have done a search of the medical literature on AD and [nonsteroidal anti-inflammatory drug] use and have discovered that the drugs being used in this study are not only unlikely to be effective but have the potential to inflict harm on these otherwise healthy individuals," Public Citizen states in a Sept. 4 letter to HHS Secretary Tommy Thompson.

The NIH National Institute on Aging-sponsored "Alzheimer's Disease Anti-Inflammatory Prevention Trial" (ADAPT) compares Celebrex (celecoxib), Naprosyn (naproxen) and placebo. The trial is being conducted at six centers in the U.S. and uses the Centers for Medicare & Medicaid Services Medicare rolls to recruit subjects.

The seven-year, 2,625-patient trial was initiated in January 2001 in patients ages 70 or older who have a relative with serious age-related memory loss, senility, dementia or Alzheimer's.

While some NSAIDs (ibuprofen, indomethacin and sulindac) are thought to inhibit a protein related to the development of Alzheimer's, celecoxib and naproxen are not among those drugs, the letter maintains.

"It is possible that other NSAIDs might be beneficial, but not the ones chosen for ADAPT."

"The fact that only certain NSAIDs inhibit" gamma secretase "explains the lack of a class effect," Public Citizen declares. "It would be logical, therefore, to select NSAIDs for AD prevention based on their g-secretase inhibitory effects, not on their cyclooxygenase inhibition. Unfortunately, this was not done."

"The choice of the two drugs for ADAPT was, unfortunately, heavily influenced by pharmaceutical support rather than basic science."

Public Citizen also calls the study's informed consent documents into question, noting a number of labeled adverse events that it feels are not adequately discussed with study participants.

For example, while the consent form warns of a risk of stomach ulcers and rare occurrences of bleeding ulcers with Celebrex use, "it never mentions perforation of the GI tract" as described in labeling, Public Citizen says.

Celebrex study participants are also not told that their advanced age is an extra risk factor for kidney problems, or that "rare, severe hepatic reactions...can lead to death," as explained in labeling, the letter states.

In addition, the consent form does not warn of anemia related to Celebrex use or the need for caution in patients with a history of high blood pressure or heart failure, Public Citizen said. Clinical studies showing a delay in bone and ligament healing should also be discussed with study participants.

Public Citizen is asking that the study be halted. "The ADAPT trial should be stopped with the current 1,000 patients (out of a planned total of 2,625) and the patients enrolled should be fully informed about the extremely unlikely probability of efficacy of these two NSAIDs as well as the properties of these drugs that might put volunteers at risk of serious adverse reactions," the letter maintains.

Public Citizen also commented on CMS' involvement in recruiting patients for the study, and said that it believes the agency adequately informed beneficiaries that enrollment in the trial is voluntary.

"If the Medicare rolls and the imprimatur of HHS are to be used to recruit patients, it is of utmost importance that...the recruitment letter makes it absolutely clear that enrollment is voluntary and that one will not lose Medicare coverage if one does not enroll," the letter states.

HHS' recruiting letter tells beneficiaries "You do not have to participate in this study. Your decision to participate or not participate will have no effect on your Medicare benefit."

Merck - which markets Vioxx (rofecoxib) - and Pfizer/Pharmacia have decided not to pursue Alzheimer's disease indications for their COX-2 inhibitors (¹ Also see "Merck COX-2 Cardiovascular Safety Studies Will Enroll 30,000 Subjects" - Pink Sheet, 17 December, 2001., p. 12).

NIH Alzheimer’s Trial Based On Industry Support, Not Science – Public Citizen

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